Erectile Dysfunction Drug May Improve Brain Blood Flow and Help Prevent Dementia

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This new study, published in Circulation Research, marks a potentially pivotal step in the fight against this debilitating condition.

Dr. Alastair Webb, as Associate Professor at the Wolfson Centre for Prevention of Stroke and Dementia at Oxford University said: ‘This is the first trial to show that sildenafil gets into the blood vessels in the brain in people with this condition, improving blood flow and how responsive these blood vessels are. These two key factors are associated with chronic damage to the small blood vessels in the brain, which is the commonest cause of vascular dementia. This demonstrates the potential of this well-tolerated, widely-available drug to prevent dementia, which needs testing in larger trials’.

The significance of this research lies in its potential to transform the treatment and prevention of vascular dementia, which currently lacks specific therapies. Chronic damage to the small blood vessels in the brain is not only the leading cause of vascular dementia but also contributes to 30% of strokes and 80% of brain bleeds. High blood pressure, reduced blood flow to the brain, and impaired blood vessel function exacerbate these conditions, making the findings of this trial particularly crucial.

The OxHARP trial was a meticulously designed double-blind, placebo-controlled study involving 75 participants who had experienced a minor stroke and showed signs of mild to moderate small vessel disease. Each participant received sildenafil, a placebo, and cilostazol (a similar drug) over three-week periods in a randomised order. The study employed cardiovascular physiology tests, ultrasound, and functional MRI scans to evaluate the drugs’ effects.

Key findings include:

• Sildenafil increased blood flow in both large and small brain vessels as measured by ultrasound and MRI scans.
• Sildenafil enhanced the blood flow response to carbon dioxide, indicating improved cerebrovascular function.
• Both sildenafil and cilostazol lowered blood vessel resistance in the brain.
• Sildenafil caused fewer side effects compared to cilostazol, particularly with less incidence of diarrhoea.

Looking ahead, the next steps involve larger-scale trials to confirm these findings and explore sildenafil’s potential in preventing vascular dementia on a broader scale.

This research was generously funded by the Wellcome Trust and supported by the National Institute for Health and Care Research, with special thanks to all the partners and participants involved.

Professor Peter Rothwell, Founding Director of the Wolfson Centre for Prevention of Stroke and Dementia said: ‘Professor Webb’s findings are very encouraging and highlight the potential for preventing vascular dementia using existing drugs that target the underlying reduction in flow in the small blood vessels in the brain.’

Reference: Webb AJS, Birks J, Feakins KA, et al. Cerebrovascular Effects of Sildenafil in Small Vessel Disease: The OxHARP Trial. Circulation Research. 2024:CIRCRESAHA.124.324327. doi: 10.1161/CIRCRESAHA.124.324327

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